Erythromycins A through D, represented by formula (E),
______________________________________ ##STR2## Erythromycin R.sup.a R.sup.b ______________________________________ A --OH --CH.sub.3 B --H --CH.sub.3 C --OH --H D --H --H ______________________________________
are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection. As with other antibacterial agents, however, bacterial strains having resistance or insufficient susceptibility to erythromycin have been identified. Also, erythromycin A has only weak activity against Gram-negative bacteria. Therefore, there is a continuing need to identify new erythromycin derivative compounds which possess improved antibacterial activity, which have less potential for developing resistance, which possess the desired Gram-negative activity, or which possess unexpected selectivity against target microorganisms. Consequently, numerous investigators have prepared chemical derivatives of erythromycin in an attempt to obtain analogs having modified or improved profiles of antibiotic activity.
Morimoto et al. describes the preparation of 6-O-methyl erythromycin A in J. Antibiotics, 37:187 (1984). Morimoto et al. further discloses 6-O-alkyl erythromycin A derivatives in J. Antibiotics, 43: 286 (1990) and in U.S. Pat. No. 4,990,602.
U.S. Pat. No. 5,444,051 discloses certain 6-O-substituted-3-oxoerythromycin A derivatives. PCT application WO 97/10251, published Mar. 20, 1997, discloses intermediates useful for preparation of 6-O-methyl 3-descladinose erythromycin derivatives.
U.S. Pat. No. 5,403,923 discloses certain tricyclic 6-O-methyl erythromycin A derivatives (Asaka, TAISHO) corresponding to PCT application WO 92/09614, published Jun. 11, 1992, and U.S. Pat. No. 5,631,355 discloses certain tricyclic 6-O-methyl 3-oxo erythromycin derivatives. U.S. Pat. No. 5,527,780 discloses certain bicyclic 6-O -methyl-3-oxo erythromycin A derivatives (Agouridas, ROUSSEL) corresponding to EP application 596802, published May 11, 1994.
PCT application WO 97/17356, published May 15, 1997, discloses tricyclic 6-O-methyl erythromycin A derivatives. Certain intermediates to the present invention are disclosed in U.S. patent application Ser. No. 08/888,350 now issued as U.S. Pat. No. 5,866,549.
Certain 6-O-methyl 2-halogenated ketolides are disclosed in FR 2,742,757 published Jun. 27, 1997.